期刊
CELLS
卷 11, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/cells11040632
关键词
unfolded protein response; endoplasmic reticulum stress; liver cancer; drug resistance; transarterial chemoembolization; anthracyclins; tumor microenvironment
类别
资金
- Swedish Cancer Foundation (Cancerfonden) [20 1076PjF, 20 0175 F, CAN2018/602]
- Swedish Society for Medical Research (SSMF) [S17-0092]
- Swedish Research Council (Vetenskapsradet) [2018-03301, 2020-02367]
- Vinnova [2018-03301] Funding Source: Vinnova
- Swedish Research Council [2020-02367, 2018-03301] Funding Source: Swedish Research Council
- Formas [2020-02367] Funding Source: Formas
Hepatocellular carcinoma (HCC) is a common and deadly cancer with high drug resistance. The rapid proliferation of tumor cells and inflammatory microenvironment lead to increased protein synthesis, causing endoplasmic reticulum (ER) stress and unfolded protein response (UPR). The three branches of the ER stress signaling pathways play a significant role in drug resistance in HCC.
Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide. It is usually diagnosed in an advanced stage and is characterized by a high intrinsic drug resistance, leading to limited chemotherapeutic efficacy and relapse after treatment. There is therefore a vast need for understanding underlying mechanisms that contribute to drug resistance and for developing therapeutic strategies that would overcome this. The rapid proliferation of tumor cells, in combination with a highly inflammatory microenvironment, causes a chronic increase of protein synthesis in different hepatic cell populations. This leads to an intensified demand of protein folding, which inevitably causes an accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum (ER). This process is called ER stress and triggers the unfolded protein response (UPR) in order to restore protein synthesis or-in the case of severe or prolonged ER stress-to induce cell death. Interestingly, the three different arms of the ER stress signaling pathways have been shown to drive chemoresistance in several tumors and could therefore form a promising therapeutic target. This review provides an overview of how ER stress and activation of the UPR contributes to drug resistance in HCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据